Wrinkling modifiers

ABSTRACT

The invention relates to wrinkling modifiers and anti-aging cosmetic compositions which each comprise a guanidine derivative represented by the following general formula (1):  
                 
 
     wherein  
                 
 
     is a heterocyclic group selected from azetidine, pyrrolidine, piperidine, piperazine or morpholine, and R 1  and R 2  are the same or different from each other and independently a hydrogen atom, or an alkyl, hydroxyl, hydroxyalkyl, carboxyl, carboxyalkyl or amidino group, or a salt thereof. The cosmetic compositions are excellent in the effects of suppressing wrinkling and of removing wrinkles and give users a pleasant feeling upon use.

TECHNICAL FIELD

[0001] The present invention relates to wrinkling modifiers andanti-aging cosmetic compositions, and more particularly to anti-agingcosmetic compositions which are excellent in the effects of suppressingwrinkling and of removing or smoothing wrinkles.

BACKGROUND ART

[0002] It is a significant concern of, particularly, women to maintainthe healthy and beautiful skin. However, the condition of the skin isalways affected by factors such as humidity, ultraviolet rays, cosmeticcompositions, aging, diseases, stress and eating habits. As the resultthereof, various skin troubles such as the decrement of variousfunctions of the skin and the aging of the skin occur. Of these,wrinkles occur due to dermal aging by aging, light aging by exposure tosunbeam, or the like. More specifically, cells f or producing fibers ofthe dermis are made small and lessened by exposure to sunbeam or withthe increase in age. In particular, collagen fibers are lost to a greatextent, and so the skin is aged by degeneration of the dermis, reductionof subcutaneous adipose tissue and the like, which forms the cause ofwrinkling, relaxation, and loss of resilience.

[0003] Various compositions and methods have heretofore been proposedfor preventing or treating the aging effects such as wrinkling [JapanesePatent Application Laid-Open Nos. 185005/1987, 502546/1987, 72157/1990,288822/1990 and 41419/1995, Japanese Patent Application Laid-Open(KOHYO) No. 510542/1994 (through PCT route), etc.]. However, all ofthese proposals have not been fully satisfactory in the effect ofmodifying wrinkling (or preventing wrinkling and removing wrinkles).There has thus been a demand for development of cosmetic skin carecompositions excellent in the effect of modifying wrinkling.

[0004] It is an object of the present invention to provide wrinklingmodifiers and anti-aging cosmetic compositions which can solve theabove-described problems, are excellent in the effects of suppressingwrinkling without impairing normal dermatophysiology and removingwrinkles, and give users a pleasant feeling upon use.

DISCLOSURE OF THE INVENTION

[0005] In view of the foregoing circumstances, the present inventorshave carried out an extensive investigation with a view toward achievingthe above object. As a result, it has been found that guanidinederivatives having a specific structure or acid-addition salts thereofare excellent in the effect of modifying wrinkling and give users apleasant feeling upon use, thus leading to completion of the presentinvention.

[0006] According to the present invention, there are thus provided awrinkling modifier and an anti-aging cosmetic composition, eachcomprising a guanidine derivative represented by the following generalformula (1):

[0007] wherein

[0008] is a heterocyclic group selected from azetidine, pyrrolidine,piperidine, piperazine or morpholine, and R¹ and R² are the same ordifferent from each other and independently a hydrogen atom, or analkyl, hydroxyl, hydroxyalkyl, carboxyl, carboxyalkyl or amidino group,or a salt thereof.

[0009] According to the present invention, there is also provided acosmetic skin care composition comprising the wrinkling modifier (1) anda synthetic sphingosine derivative represented by the following generalformula (2):

[0010] wherein R³ is a linear, branched or cyclic, saturated orunsaturated hydrocarbon group having 4 to 40 carbon atoms, R⁴, R⁵, R⁶,R⁷ and R⁸ are independently a hydrogen atom or a hydrocarbon grouphaving 1 to 10 carbon atoms, which may be substituted by at least onehydroxyl group, and X and Y are independently a hydrogen atom or analkyl group having 1 to 6 carbon atoms, which may contain at least oneoxygen atom in its structure.

BEST MODE FOR CARRYING OUT THE INVENTION

[0011] Among the heterocyclic groups represented by

[0012] in the general formula (1) which represents the guanidinederivatives or the salts thereof used in the present invention,pyrrolidine, piperidine, piperazine and morpholine are preferred. Thealkyl groups represented by R¹ and R² include linear or branched alkylgroups having 1 to 6 carbon atoms. Of these, alkyl groups having 1 to 4carbon atoms are preferred. Specific examples of the alkyl groupsinclude methyl, ethyl, n-propyl and isopropyl groups. Of these, methylgroup is particularly preferred. The hydroxyalkyl groups includehydroxyalkyl groups having 1 to 6 carbon atoms, and hydroxyalkyl groupshaving 1 to 4 carbon atoms are preferred. Specific examples of thehydroxyalkyl groups include hydroxymethyl, hydroxyethyl andhydroxypropyl groups, with the hydroxymethyl and hydroxyethyl groupsbeing particularly preferred. The carboxyalkyl groups includecarboxyalkyl groups having 2 to 7 carbon atoms, and carboxyalkyl groupshaving 2 to 5 carbon atoms are preferred. Specific examples of thecarboxyalkyl groups include carboxymethyl, carboxyethyl, carboxypropyland carboxybutyl groups, with the carboxymethyl and carboxyethyl groupsbeing particularly preferred.

[0013] R¹ and R² may be the same or different from each other and be anoptional combination of 2 groups.

[0014] Stereoisomers exist in the guanidine derivatives (1) because ofthe presence of asymmetric carbon atoms. In the present invention, allthese stereoisomers and mixtures thereof may be used.

[0015] Specific examples of the guanidine derivatives (1) includeN-amidinoproline, 2-hydroxymethyl-1-pyrrolidine-carboxamidine,3-hydroxy-1-pyrrolidinecarboxamidine, N-amidinoaziridine-2-carboxylicacid, N-amidino-2-piperidinecarboxylic acid,N-amidino-3-piperidine-carboxylic acid, N-amidino-4-piperidinecarboxylicacid, N-amidino-4-piperidinepropionic acid, pyrrolidine-carboxamidine,piperidinecarboxamidine, 2-methyl-piperidinecarboxamidine,3-methylpiperidinecarboxamidine, 4-methylpiperidinecarboxamidine,2-methylmorpholine-carboxamidine, 3-methylmorpholinecarboxamidine,N-methyl-piperazinecarboxamidine,N-2-hydroxyethylpiperazine-carboxamidine and piperazinecarboxamidine.

[0016] An acid for forming salts of the guanidine derivatives (1) may beeither an organic acid or an inorganic acid. Examples thereof includemonocarboxylic acids such as formic acid, acetic acid, propionic acid,butyric acid, isobutyric acid, hexanoic acid, heptanoic acid, octanoicacid, nonanoic acid, decanoic acid, lauric acid, myristic acid, palmiticacid, stearic acid, acrylic acid, methacrylic acid, crotonic acid,isocrotonic acid, phenylacetic acid, cinnamic acid, benzoic acid, sorbicacid, nicotinic acid, urocanic acid and pyrrolidone-carboxylic acid;dicarboxylic acids such as oxalic acid, malonic acid, succinic acid,glutamic acid, adipic acid, pimelic acid, cork acid, azelaic acid,sebacic acid, maleic acid, fumaric acid, phthalic acid and terephthalicacid; hydroxy acids such as glycolic acid, lactic acid, malic acid,tartaric acid, citric acid and o-, m- or p-hydroxybenzoic acid; aminoacids such as glycine, alanine, β-alanine, valine, leucine,phenylalanine, tyrosine, serine, threonine, methionine, cysteine,cystine, proline, hydroxyproline, pipecolic acid, triptophan, asparticacid, asparagin, glutamic acid, glutamine, lysine, histidine, ornithine,arginine and aminobenzoic acid; lower alkyl-sulfonic acids such asmethanesulfonic acid and trifluoro-methanesulfonic acid; arylsulfonicacids such as benzene-sulfonic acid and p-toluenesulfonic acid;hydrohalogenic acids such as hydrofluoric acid, hydrochloric acid,hydrobromic acid and hydriodic acid; and inorganic acids such asperchloric acid, sulfuric acid, nitric acacia, phosphoric acid andcarbonic acid.

[0017] The guanidine derivatives (1) or the salts thereof can beobtained in accordance with, for example, a preparation processrepresented by the following reaction scheme:

[0018] wherein

[0019] R¹ and R² have the same meanings defined above.

[0020] More specifically, a cyclic amine derivative (3) is reacted witha guanidylating reagent, whereby a guanidine derivative (1) or a saltthereof can be obtained.

[0021] Examples of the guanidylating reagent include known guanidylatingreagents such as cyanamides, S-alkyl-isothioureas, O-alkylisoureas,aminoiminomethanesulfonic acid, 3,5-dimethyl-1-guanylpyrazole,1H-pyrazole-1-carbamidine.

[0022] In the case where an S-alkylisothiourea, O-alkyl-isourea,3,5-dimethyl-1-guanylpyrazole or 1H-pyrazole-1-carbamidine is used, thereaction may be conducted by stirring the reactants at 0 to 200° C. for1 to 72 hours in the presence or absence of a base such as bariumhydroxide, calcium hydroxide, magnesium hydroxide, sodium hydroxide,potassium hydroxide, lithium hydroxide, sodium hydrogen-carbonate,sodium carbonate, aqueous ammonia, a tertiary amine such astriethylamine, N,N-dimethylaniline, N,N′-dimethylpiperazine orN-methylpiperidine, or pyridine. In the case where a cyanamide is used,it is only necessary to stir the reactants at 0 to 200° C. for 1 to 72hours, or stir the reactants at 25 to 200° C. for 1 to 72 hours in thepresence of any one of the acids exemplified for the formation of thesalts of the guanidine derivatives.

[0023] After completion of the reaction, as needed, the acid may beadded to the reaction product in accordance with a method known per sein the art to isolate it as an acid-addition salt.

[0024] The guanidine derivatives (1) or the salts thereof may be usedeither singly or in any combination thereof. The amount of such acompound incorporated in the wrinkling modifiers and the cosmeticcompositions is preferably 0.001 to 50% by weight. It is particularlypreferred that it be incorporated in an amount of 0.001 to 30% byweight, more preferably 0.01 to 20% by weight, since the feeling uponuse is improved, to say nothing of the wrinkling-modifying effect.

[0025] The synthetic sphingosine derivative is represented by theformula (2). Examples of the linear, branched or cyclic, saturated orunsaturated hydrocarbon group having 4 to 40 carbon atoms represented byR³ in the general formula (2) include alkyl groups such as n-butyl,sec-butyl, pentyl, hexyl, octyl, 2-ethylhexyl, decyl, dodecyl,tetradecyl, pentadecyl, hexadecyl, octadecyl,5,7,7-trimethyl-2-(1,3,3-trimethylbutyl)octyl, 2-heptylundecyl andmethyl-branched isostearyl groups; alkenyl groups such as butenyl,hexenyl, oleyl, 9-octadecenyl, 9,12-octadeca-dienyl,3,7-dimethylocta-2,6-dienyl and 3,7,11-trimethyl-2,6,10-dodecatrienylgroups; cycloalkyl groups such as cyclopentyl and cyclohexyl groups; andaryl groups such as phenyl, tolyl and naphthyl groups.

[0026] In the present invention, the linear or branched, saturatedhydrocarbon groups having 4 to 40 carbon atoms are preferred. Of these,tetradecyl, octadecyl and methyl-branched isostearyl groups areparticularly preferred.

[0027] The hydrocarbon groups having 1 to 10 carbon atoms represented byR⁴ to R⁸, which may be substituted by at least one hydroxyl group,include alkyl groups and mono-,di- or tri-hydroxyalkyl groups such asmethyl, ethyl, n-propyl, isopropyl, hydroxymethyl, hydroxyethyl,2-hydroxy-ethyl and 3,3,3-trihydroxypropyl groups. However, a hydrogenatom or methyl group is preferred as each of R⁴ to R⁸.

[0028] Examples of the alkyl groups having 1 to 6 carbon atomsrepresented by X and Y, which may contain at least one oxygen atom intheir structures, include glucosyl, fructosyl, galactosyl, mannosyl,methyl, ethyl, propyl, hexyl, 2-hydroxyethyl, 3-hydroxyethyl,4-hydroxypropyl, 5-hydroxy-6-hydroxybutyl, 2,3-dihydroxypropyl,2-(1,2,3-trihydroxypropyl)methyl and3-(2,3-dihydroxypropyloxy)-2-hydroxyethyl groups. However, a hydrogenatom or 2-hydroxyethyl group is particularly preferred as each of X andY.

[0029] These sphingosine derivatives may be used either singly or in anycombination thereof. The amount of such a derivative incorporated in thecosmetic compositions is preferably 0.0001 to 10% by weight. It isparticularly preferred that it be incorporated in an amount of 0.001 to2% by weight, since the feeling upon use is improved, to say nothing ofthe wrinkling-modifying effect.

[0030] Into the wrinkling modifiers and the cosmetic compositionsaccording to the present invention, may be further incorporated anorganic acid, an inorganic acid such as phosphoric acid, sulfuric acidor hydrochloric acid, or an ester thereof. The incorporation of such acompound is preferred because the wrinkling-modifying effect can be moreenhanced.

[0031] No particular limitation is imposed on the organic acid or theester thereof so far as it is not included in the guanidine derivatives(1). For example, α- or β-hydroxycarboxylic acids, dicarboxylic acids,fatty acids and esters thereof may be mentioned. One or more of thesecompounds may be incorporated. Examples of these organic acids includethose represented by the following formulae (4) to (6), and estersthereof.

 R⁹(CR¹⁰OH)_(q)(CH₂)_(r)COOH  (5)

[0032] In the formula (4), Y¹ is a hydrogen atom or CH₃(C₁H_(m))_(n) (lbeing an integer of 1 to 27, m being an integer of 2 to 54, and n being0 or 1). In the formula (5), R⁹ and R¹⁰ are independently a hydrogenatom, a saturated or unsaturated, branched, linear or cyclic alkyl grouphaving 1 to 25 carbon atoms, an aralkyl group or an aryl group, q is aninteger of 1 to 9, and r is an integer of 0 to 23. In the formula (6), sis an integer of 0 to 9, and t is an integer of 0 to 23. More specificexamples of the organic acids include ascorbic acid, ε-aminocaproicacid, erythorbic acid, citric acid, succinic acid, tartaric acid, sorbicacid, dehydroacetic acid, lactic acid, urocanic acid, edetic acid,hydroxybenzonesulfonic acid, orotic acid, capric acid, glycolic acid,cerotic acid, nicotinic acid, hydroxyethanediphosphonic acid, phyticacid, fumaric acid, malic acid, levulinic acid, acrylic acid andoligomers or polymers thereof, and esters thereof.

[0033] Examples of the fatty acids include linolic acid, γ-linolenicacid, columbinic acid, icosa-(η-6,9,13)-trienoic acid, arachidonic acid,α-linolenic acid, thymunodonic acid, hexanoic acid, isostearic acid,undecylenic acid, stearic acid, palmitic acid, behenic acid, myristicacid, coconut oil fatty acid, lauric acid, lanolinic acid and DHA, andbesides hydroxy fatty acids such as 12-hydroxystearic acid. Theinorganic acids or the esters thereof include monoalkylphosphoric acidssuch as cetylphosphoric acid, and dialkylphosphoric acids.

[0034] In the present invention, among these organic acids and inorganicacids, the organic acids represented by the formulae (4), (5) and (6)are preferred. The dicarboxylic acids represented by the formula (6) aremore preferred, with succinic acid being particularly preferred becausethe wrinkling-modifying effect can be more enhanced. The organic acid,inorganic acids and the like may be used either singly or in anycombination thereof. The amount of such an acid incorporated in thewrinkling modifiers and the cosmetic compositions is preferably 0.001 to30% by weight. It is particularly preferred that it be incorporated inan amount of 0.005 to 20% by weight, more preferably 0.01 to 10% byweight, since the feeling upon use is improved, to say nothing of thewrinkling-modifying effect. An incorporating ratio of the organic acid,inorganic acid or the like to the guanidine derivative or theacid-addition salt thereof is preferably 0.5:99.5 to 99.5:0.5 in termsof weight ratio. It is particularly preferred that the ratio be 5:95 to95:5, since the wrinkling-modifying effect can be more enhanced.

[0035] Into the wrinkling modifiers and the cosmetic compositionsaccording to the present invention, may be further incorporated an oilysubstance. No particular limitation is imposed on the oily substance,and examples thereof include hydrocarbons such as solid and liquidparaffins, crystal oil, ceresin, ozocerite, montan wax, squalane andsqualene; ester oils such as olive oil, carnauba wax, lanolin, jojobaoil, glyceryl monostearate, glyceryl distearate, glyceryl monooleate,isopropyl stearate, neopentylglycol dicaprate and glycerol isostearate;higher alcohol such as cetanol and stearyl alcohol; and naturallyextracted sphingosine derivatives and synthetic ceramide derivativesrepresented by the following general formula (7):

[0036] wherein R¹¹ is a linear or branched, saturated or unsaturatedhydrocarbon group having 10 to 26 carbon atoms, R¹² is a linear orbranched, saturated or unsaturated hydrocarbon group having 9 to 25carbon atoms, and A and B are independently a hydrogen atom or a sugarresidue. One or more of these oily substances may be used.

[0037] When these oily substances are incorporated, they are preferablyincorporated in a proportion of 0.001 to 50% by weight, particularlypreferably 0.005 to 30% by weight into the wrinkling modifiers and thecosmetic compositions.

[0038] Into the wrinkling modifiers and the cosmetic compositionsaccording to the present invention, may be further incorporated asterol. Examples of the sterol include cholesterol, provitamin D₃,campesterol, stegmastanol, stegmasterol, 5-dihydrocholesterol,α-spinasterol, palysterol, clionasterol, γ-sitosterol, stegmastenol,sargasterol, apenasterol, ergostanol, sitosterol, colubisterol,chondrillasterol, polyphellasterol, haliclonasterol, neospongosterol,fucosterol, aptostanol, ergostadienol, ergosterol, 22-dihydroergosterol,brassicasterol, 24-methylene-cholesterol, 5-dihydroergosterol,dehydroergosterol, fungisterol, cholestenol, coprostenol, zymosterol,7-hetocholesterol, lathosterol, 22-dehydrocholesterol, β-sitosterol,cholestatrien-3β-ol, coprostanol, cholestanol, ergostenol,7-dehydrocholesterol, 24-dehydrocholestadion-3β-ol, equilenine, equilin,estrone, 17β-estradiol, androst-4-ene-3 β,17β-diol anddehydroepiandrosterone. One or more of these sterols may be used.

[0039] When these sterols are incorporated, they are preferablyincorporated in a proportion of 0.001 to 50% by weight, particularlypreferably 0.005 to 30% by weight into the cosmetic skin carecompositions.

[0040] Into the wrinkling modifiers and the cosmetic compositionsaccording to the present invention, may be further incorporated asurfactant. Examples of the surfactant include polyoxyethylene alkylethers, polyoxyethylene fatty acid esters, polyoxyethylene sorbitanfatty acid esters, polyoxyethylene sorbitol fatty acid esters, glycerolfatty acid esters, polyoxyethylene hardened castor oil alkylsulfates,polyoxyethylene alkylsulfates, alkylphosphates, polyoxyethylenealkylphosphates, alkali metal salts of fatty acids, sorbitan fatty acidesters, glycerol fatty acid esters and alkyl glyceryl ethers. One ormore of these surfactants may be used.

[0041] When these surfactants are incorporated, they are preferablyincorporated in a proportion of 0.001 to 50% by weight, particularlypreferably 0.005 to 30% by weight into the wrinkling modifiers and thecosmetic compositions.

[0042] Into the wrinkling modifiers and the cosmetic compositionsaccording to the present invention, may be further incorporated awater-soluble polyhydric alcohol. Examples of the water-solublepolyhydric alcohol include alcohols having two or more hydroxyl groupsin their molecules, for example, ethylene glycol, propylene glycol,1,3-butylene glycol, 1,4-butylene glycol, dipropylene glycol, glyceroland polyglycerols such as diglycerol, triglycerol and tetraglycerol,glucose, maltose, maltitol, sucrose, fructose, xylitol, sorbitol,maltotriose, threitol, erythritol, and alcohols obtained by reduction ofamylolytic sugar. One or more of these alcohols may be used.

[0043] When these water-soluble polyhydric alcohols are incorporated,their proportion in the wrinkling modifiers and the cosmeticcompositions may be suitably determined according to the preparationforms of the modifiers and the cosmetic compositions. However, it isgenerally preferred to incorporate them in a proportion of 0.001 to 75%by weight, particularly preferably 0.1 to 25% by weight.

[0044] Into the wrinkling modifiers and the cosmetic compositionsaccording to the present invention, may be further incorporated powder.Examples of the powder include extenders such as mica, talc, sericite,kaolin, nylon powder and polymethylsil sesquioxane; inorganic pigmentssuch as pearl; organic pigments such as Red Color No. 202, Red Color No.226, Yellow Color No. 4 and aluminum lake; and inorganic powders forultraviolet screening, such as zinc oxide, titanium oxide, zirconiumoxide and iron oxide. These powders may be subjected to a siliconetreatment with methyl hydrogenmethylpolysiloxane, trimethylsiloxysilicicacid, methylpolysiloxane or the like, a fluorine treatment with aperfluoroalkyl phosphate, perfluoroalcohol or the like, an amino acidtreatment with N-acylglutamic acid or the like, a lecithin treatment, ametal soap treatment, a fatty acid treatment, an alkylphosphatetreatment, or the like before their use.

[0045] When these powders are incorporated, their proportion in thewrinkling modifiers and cosmetic compositions may be suitably determinedaccording to the preparation forms of the modifiers and the cosmeticcompositions. However, it is generally preferred to incorporate them ina proportion of 0.001 to 50% by weight, particularly preferably 0.005 to30% by weight.

[0046] Into the wrinkling modifiers and the cosmetic compositionsaccording to the present invention, may be further incorporated asilicone. No particular limitation is imposed on the silicone so far asit is that commonly incorporated into the classical cosmeticcompositions. Examples thereof include octamethylpolysiloxane,tetradecamethylpolysiloxane, methylpolysiloxane, high-polymericmethylpolysiloxane and methylphenylpolysiloxane, and besidesmethylpolycyclosiloxanes such as octamethylcyclotetrasiloxane anddecamethylcyclopenta-siloxane, trimethylsiloxysilicic acid, and modifiedsilicones such as polyether alkyl-modified silicone and alkyl glycerylether-modified silicone.

[0047] When these silicones are incorporated, their proportion in thewrinkling modifiers and the cosmetic compositions may be suitablydetermined according to the preparation forms of the modifiers and thecosmetic compositions. However, it is generally preferred to incorporatethem in a proportion of 0.001 to 50% by weight, particularly preferably0.005 to 30% by weight.

[0048] Into the wrinkling modifiers and the cosmetic compositionsaccording to the present invention, various ingredients commonlyincorporated into the classical cosmetics, quasi-drugs, drugs and thelike may be incorporated so far as no detrimental influence is therebyimposed on the objects of the present invention. Examples of suchingredients include inorganic salts such as magnesium sulfate, potassiumsulfate, sodium sulfate, magnesium chloride and sodium chloride;viscosity modifiers such as polyvinyl alcohol, carboxyvinyl polymers,carboxymethyl cellulose, gelatin, tragacanth gum, xanthan gum,hyaluronic acid, tuberose extract, agarose and sodium alginate; andbesides antiseptics such as parabens, pH adjusters, wetting agents,ultraviolet absorbents, coloring matter, medicinally-effectiveingredients and perfume bases.

[0049] The wrinkling modifiers and the cosmetic compositions accordingto the present invention are preferably at a pH of 2 to 11. It isparticularly preferred that the pH be at 3 to 10, since the normalphysiological function of the skin can be retained. The wrinklingmodifiers and the cosmetic compositions according to the presentinvention can be prepared in accordance with a method known per se inthe art, formulated into any desired forms such as emulsions,dispersions, two-layer compositions, solutions and gel, and provided astoilet waters, milky lotions, creams, packs, paps, foundations and thelike.

EXAMPLES

[0050] The present invention will hereinafter be described in moredetail by the following examples. However, the present invention is notlimited by these examples.

[0051] The following Compounds (1) to (16) were used as the guanidinederivatives or the salts thereof to evaluate them as to thewrinkling-modifying effect.

Effect of the Guanidine Derivatives (1) to (16) on Wrinkles Formed onHairless Mice by Exposure to UVB

[0052] (1) Hairless mice (HR/ICR, aged 6 weeks at the beginning of theexperiment) were,exposed to UVB 3 times a week by using 6 Toshibahealthy lamps, 20SE. The amount of energy was measured by means of aUV-Radiometer, UVR-305/365D manufactured by TOKYO OPTICAL K.K. The doseupon one exposure was determined to be 1 MED or less, i.e., 65 mJ in anamount of energy of 0.28 mW/cm². The exposure was effected for 20 weeks.After confirming that the hairless mice had got wrinkles at their backs,they were divided into groups each consisting of 8 mice. Aqueous ethanol(water/ethanol=50/50 vol. %) solutions separately containing Compounds(1) to (16) at a concentration of 4% were applied 5 times a week totheir corresponding groups of mice over 6 weeks in a dose of 100 μl. Asa control, aqueous ethanol (water/ethanol=50/50 vol. %) was applied in adose of 100 μl like the samples. After completion of the application,the degree of wrinkles was visually observed to evaluate the samples inaccordance with the following standard (wrinkle index). The results areshown in Table 1.

[0053] (Wrinkle index)

[0054] 1: Wrinkles were completely removed or smoothed;

[0055] 2: Wrinkles were scarcely observed;

[0056] 3: Wrinkles were somewhat observed;

[0057] 4: Wrinkles were observed to a great extent.

[0058] (2) In order to further analyze the particulars of wrinkles, skinreplicas of the size of 14 mm in diameter were gathered from a portionof the back in each of the mice using a Hydrophilic Exaflex hydrophilicvinylsilicone impression material. Each of these replicas was heldhorizontally and illuminated at an angle of 30 degrees from thehorizontal direction, thereby finding a proportion of shadows of thewrinkles as an area percent by means of an image analyzer. The resultsare shown in Table 1. TABLE 1 Area percent by image Compound Wrinkleindex analysis (%) Control 3.73 10.6 Compound (1) 2.0 3.21 Compound (2)2.125 2.48 Compound (3) 2.50 4.32 Compound (4) 2.50 5.37 Compound (5)2.75 4.76 Compound (6) 2.75 3.51 Compound (7) 2.75 4.28 Compound (8)2.25 3.26 Compound (9) 2.375 4.00 Compound (10) 2.50 3.41 Compound (11)2.75 4.02 Compound (12) 2.50 3.62 Compound (13) 2.375 4.30 Compound (14)2.125 3.62 Compound (15) 2.50 4.48 Compound (16) 2.25 4.25

[0059] As apparent from Table 1, the wrinkles formed on the backs of thehairless mice can be removed by applying any of the guanidinederivatives (1) to (16) thereto.

EXAMPLE 2

[0060] Compounds (17) to (21) in which the definitions of the respectivesymbols in the general formula (2) are as shown in Table 2 were used asthe synthetic sphingosine derivatives to evaluate them as to thewrinkling-modifying effect in accordance with the same process as inExample 1. The experiment was conducted at concentrations of 5% for theguanidine derivatives and 0.5% for the synthetic sphingosinederivatives. TABLE 2 Compound R³ R⁴ R⁵—R⁸ X Y Compound (17) Methyl- H HH H branched isostearyl Compound (18) Methyl- CH₃ H H H branchedisostearyl Compound (19) Tetradecyl H H H H Compound (20) Octadecyl CH₃H H H Compound (21) Methyl- H H —CH₂—CH₂—OH H branched isostearyl

[0061] TABLE 3 Guanidine Sphingosine Wrinkle Area percent by derivativederivative index image analysis (%) Not used Not used 3.75 10.2 Compound(1) Compound (17) 2.25 3.73 Compound (2) Compound (17) 2.75 4.03Compound (4) Compound (17) 2.75 3.88 Compound (5) Compound (17) 1.752.40 Compound (6) Compound (17) 2.125 2.39 Compound (1) Compound (18)2.5 3.60 Compound (1) Compound (18) 2.75 3.97 Compound (2) Compound (19)2.375 3.45 Compound (2) Compound (19) 2.125 3.26 Compound (8) Compound(20) 2.25 4.14 Compound (9) Compound (21) 2.0 2.78

[0062] As apparent from Table 3, the wrinkles formed on the backs of thehairless mice can be removed by the cosmetic skin care compositionscomprising the guanidine derivative and the sphingosine derivative.

[0063] The following wrinkling-modifying cosmetic compositions wereprepared. (Components) (% by weight) Example 3: Cream Stearic acid 2.00Squalane 2.00 Cholesterol 3.00 Olive oil 1.00 Cetanol 7.00 Jojoba oil2.00 Arginine 2-hexadecylphosphate 2.00 Polyoxyethylene (40 EO) hardenedcastor oil 0.50 Glycerol 10.00 1,3-Butylene glycol 5.00 Compound (1)5.00 Succinic acid 1.00 Purified water Balance Total 100.00 Example 4:Gel Polyoxyethylene (20 EO) isocetyl ether 1.00 Sodium polyoxyethylene(10 EO) trialkyl- 1.00 phosphate Sorbitol 0.50 1,3-Propanediol 0.50Xanthan gum 0.50 Tuberose polysaccharide 3.00 Carboxyvinyl polymer(Carbopol 940, product 0.20 of Goodrich Co.) Allantoin 0.10 Zincsulfocarbolate 0.20 Compound (1) 10.00 Ethanol 20.00 Antiseptic Properamount Perfume base Proper amount Purified water Balance Total 100.00Example 5: Gel Silicone composition (XSG-16, product of 5.00 Shin-EtsuChemical Co., Ltd.) Methylpolysiloxane (KF96A-6cs, product of 15.00Shin-Etsu Chemical Co., Ltd.) Methylpolysiloxane (SH244, product of 5.00Dow Corning Toray Silicone Co., Ltd.)Methylpolysiloxane.methyl(polyoxyethylene)- 2.00 siloxane copolymer(SH3771C, product of Dow Corning Toray Silicone Co., Ltd.)Methylpolysiloxane.methyl(polyoxyethylene)- 1.00 siloxane copolymer(SH3775C, product of Dow Corning Toray Silicone Co., Ltd.) Methylcellulose 0.20 Hydroxyethyl cellulose hydroxypropyltrimethyl- 0.02ammonium chloride ether (Caticelo H-60, product of Kao Corporation)dl-α-Tocopherol acetate 0.05 Isostearyl glycyrrhetinate 0.10Isopropylmethylphenol 0.10 Zinc white 1.50 Compound (1) 7.00 Compound(17) 0.50 Ethanol 5.00 Antiseptic Proper amount Perfume base Properamount Purified water Balance Total 100.00 Example 6: Toilet waterArginine 0.40 Lysine 0.40 Polyoxyethylene (40 EO) hardened castor oil1.50 Methylpolysiloxane·methyl(polyoxyethylene)- 0.60 siloxane copolymer(SH3775C, product of Dow Corning Toray Silicone Co., Ltd.) Glycerol 5.00Glycinebetaine 0.20 Trisodium citrate 0.90 Citric acid 0.40 Urea 0.50ε-Aminocaproic acid 0.10 Compound (1) 5.00 Compound (17) 0.50 Ethanol5.00 Antiseptic Proper amount Perfume base Proper amount Purified waterBalance Total 100.00 Example 7: Toilet water Triethanolamine 0.40Potassium hydroxide 0.20 Polyoxyethylene (20 EO) isocetyl ether 0.30Sodium polyoxyethylene (8 EO) oleyl ether 0.30 phosphate Sodiumpolyoxyethylene (10 EO) dialkyl- 0.10 phosphate Polyethylene glycol 15002.00 Polyoxyethylene (10 EO) methylglycoside 1.50 Dipropylene glycol0.50 Disodium hydrogenphosphate 0.50 Succinic acid 0.30 Compound (1)7.00 Ethanol 10.00 Antiseptic Proper amount Perfume base Proper amountPurified water Balance Total 100.00 Example 8: Pack Polyvinyl alcohol(Gohsenol EG-30, product 15.00 of The Nippon Synthetic Chemical IndustryCo., Ltd.) Aqueous solution of carboxymethylchitin 5.00 (Chitin LiquidHV-10, product of Ichimaru Pharcos Co., Ltd.) Triglucopolysaccharide(Pullulan PI-20, 0.50 product of Hayashibara Company, Ltd.) Xanthan gum0.50 Sodium carboxymethyl cellulose 0.50 Titanium oxide 15.00 Aluminummagnesium silicate 1.00 1-Isostearoyl-3-myristoylglycerol 1.00Diglycerol 1.50 Polyoxyethylene (20 EO) isocetyl ether 1.00 Compound (1)7.00 Compound (14) 0.70 Ethanol 5.00 Antiseptic Proper amount Perfumebase Proper amount Purified water Balance Total 100.00 Example 9: Milkylotion Palmitic acid 0.50 Olive oil 2.00 Cetanol 1.00 Jojoba oil 5.00Sodium monohexadecylphosphate 2.00 Sorbitan monostearate 0.50 Glycerol15.00 Ethanol 5.00 Compound (2) 10.00 Compound (17) 0.30 Lactic acid2.00 Purified water Balance Total 100.00 Example 10: Milky lotionN-(3-Hexadecyloxy-2-hydroxypropyl)-N-2- 0.50 hydroxyethyldecanamideN-(3-Hexadecyloxy-2-hydroxypropyl)-N-2- 1.00 hydroxyethylhexadecanamideN-(3-Tetradecyloxy-2-hydroxypropyl)-N-2- 0.50 hydroxyethyldecanamidePolyoxyethylene (10 EO) hardened castor oil 1.00Methylpolysiloxane.methyl(polyoxyethylene)- 1.00 siloxane copolymer(SH3775C, product of Dow Corning Toray Silicone Co., Ltd.) Sorbitanmonostearate 0.20 Sodium stearoylmethyltaurine 0.50 Cholesterol 0.80Cholesterol isostearate 0.20 Stearic acid 0.20 Palmitic acid 0.30Myristic acid 0.10 Pentyl glycol dicaprate 4.00 Methylpolysiloxane(KF96A-500cs, product of 2.00 Shin-Etsu Chemical Co., Ltd.) Isostearylalcohol 1.20 Cetyl alcohol 1.00 Glycerol 3.50 Lactic acid 0.20 Sodiumlactate 0.30 Compound (2) 5.00 Antiseptic Proper amount Perfume baseProper amount Purified water Balance Total 100.00 Example 11: Papα-Monoisostearyl glyceryl ether 1.00 Pentyl glycol neocapratemethylpolysiloxane 4.00 Glycerol 35.00 Purified water 15.80 Sodiumpolyacrylate 5.50 Aluminum potassium sulfate 1.00 Aqueous solution (10%)of polyacrylic acid 15.00 Precipitated silicic acid anhydride 2.00Compound (1) 10.00 Compound (17) 0.20 Purified water Balance Total100.00

Industrial Applicability

[0064] The wrinkling modifiers and the cosmetic compositions accordingto the present invention are excellent in the effects of suppressingwrinkling and of removing wrinkles and give users a pleasant feelingupon use.

1. A wrinkling modifier comprising a guanidine derivative represented bythe following general formula

wherein

is a heterocyclic group selected from azetidine, pyrrolidine,piperidine, piperazine or morpholine, and R¹ and R² are the same ordifferent from each other and independently a hydrogen atom, or analkyl, hydroxyl, hydroxyalkyl, carboxyl, carboxyalkyl or amidino group,or a salt thereof.
 2. The wrinkling modifier according to claim 1,wherein the guanidine derivative or the salt thereof is contained in anamount of 0.001 to 50% by weight.
 3. The wrinkling modifier according toclaim 1 or 2, which further comprises an organic acid, an inorganic acidor an ester thereof.
 4. The wrinkling modifier according to claim 3,wherein the organic acid, the inorganic acid or the ester thereof iscontained in an amount of 0.001 to 30% by weight.
 5. An anti-agingcosmetic composition comprising the guanidine derivative or the saltthereof according to claim
 1. 6. The anti-aging cosmetic compositionaccording to claim 5, wherein the guanidine derivative or the saltthereof is contained in an amount of 0.001 to 50% by weight.
 7. Theanti-aging cosmetic composition according to claim 5 or 6, which furthercomprises an organic acid, an inorganic acid or an ester thereof.
 8. Theanti-aging cosmetic composition according to claim 7, wherein theorganic acid, the inorganic acid or the ester thereof is contained in anamount of 0.001 to 30% by weight.
 9. A cosmetic skin care compositioncomprising the wrinkling modifier according to claim 1 and a syntheticsphingosine derivative represented by the following general formula (2):

wherein R³ is a linear, branched or cyclic, saturated or unsaturatedhydrocarbon group having 4 to 40 carbon atoms, R⁴, R⁵, R⁶, R⁷ and R⁸ areindependently a hydrogen atom or a hydrocarbon group having 1 to 10carbon atoms, which may be substituted by at least one hydroxyl group,and X and Y are independently a hydrogen atom or an alkyl group having 1to 6 carbon atoms, which may contain at least one oxygen atom in itsstructure.
 10. The cosmetic skin care composition according to claim 9,wherein the wrinkling modifier and the synthetic sphingosine derivativeare contained in amounts of 0.001 to 50% by weight and 0.0001 to 10% byweight, respectively.
 11. The cosmetic skin care composition accordingto claim 9 or 10, which further comprises an organic acid, an inorganicacid or an ester thereof.
 12. The cosmetic skin care compositionaccording to claim 11, wherein the organic acid, the inorganic acid orthe ester thereof is contained in an amount of 0.001 to 30% by weight.